Biology subjects

Gonzalez-Gonzalez, E.

Publications and source records attributed to Gonzalez-Gonzalez, E..

3 recordsLinked to original sources

bioRxiv2025

Evidence for Toxin-Encoding Coinfections Driving Intransitive Dynamics Between Allelopathic Phenotypes in Natural Yeast Populations

Competitive intransitivity -- non-hierarchical interactions, such as those exemplified by the rock-paper-scissors game, where no single competitor wins outright -- has been proposed as a key mechanism for maintaining biodiversity; however, empirical evidence supporting the importance of intransitivity remains limited. Natural populations of Saccharomyces cerevisiae often include strains harboring totivirus-satellite coinfections that encode a lethal toxic glycoprotein capable of eliminating competing yeast strains. Killer strains are sparsely distributed in natural populations, despite their competitive advantage. Yeast isolates occasionally exhibit toxin resistance, but it remains untested whether they can outcompete and replace killer strains. Similarly, the persistence of toxin-susceptible yeast is not well understood --particularly whether they can invade resistant populations in the absence of killers, thereby completing an intransitive loop. In a multi-year collection of yeast isolates from vineyards across New Zealand, we observed a near-complete disappearance of a previously common killer yeast genotype of S. cerevisiae over consecutive years. Using space-time-shift competition assays, we demonstrate that strains sympatric to this killer genotype were ubiquitously resistant, unlike the allopatric strains that were frequently eliminated in competition assays. Furthermore, the extinction of the focal killer genotype appears to have enabled the emergence of toxin-susceptible competitors in sites formerly occupied by the killer genotype. Our findings suggest that the competitive advantage of toxin production is evident in natural populations but appears to be eroded when resistance evolves in competitors of the focal killer genotype. We suggest that such killer-resistant-susceptible polymorphisms are being maintained by evolutionary dynamics akin to rock-paper-scissors-like intransitivity, driven by the invasion of susceptible strains after costly resistance has driven killer strains to extinction in natural populations, all being driven by toxin-encoding coinfections.

evolutionary biology↗

bioRxiv2025

Addressing SARS-CoV-2 Evolution: Neutralization of Emerging Variants of Concern by the AVX/COVID-12 'Patria' Vaccine Based on HexaPro-S Ancestral Wuhan Spike or Its Updated BA.2.75.2 Version

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global health challenge, causing severe morbidity and mortality, particularly in vulnerable groups such as the elderly, immunocompromised individuals, and those with comorbidities. In low- and middle-income countries (LMICs), vaccine access is hindered by high costs and inequitable distribution. To tackle these issues, Mexico developed the AVX/COVID-12 (V-Wu) vaccine, a recombinant Newcastle disease virus (NDV)-based platform expressing a stabilized ancestral Wuhan spike protein (HexaPro-S). Locally manufactured after rigorous testing and regulatory approval, V-Wu aims to enhance self-sufficiency and equity in immunization. This study evaluates an updated vaccine version, AVX/COVID-12 (V-BA), designed to combat Omicron subvariants by expressing the HexaPro-S protein of BA.2.75.2. Both vaccines were administered intramuscularly in K18-hACE2 transgenic and BALB/c mouse models using a prime-boost regimen. Immunogenicity was analyzed by measuring antibodies against Omicron S proteins BA.2.75.2 and XBB.1.5, as well as neutralizing antibodies against Wuhan, BA.1, XBB.1.16, and JN.1 variants. Both vaccines were safe, eliciting robust antibody responses against Omicron S proteins and neutralizing antibodies against multiple emerging SARS-CoV-2 variants of concern (VOCs). V-BA demonstrated superior protection against current Omicron variants, while V-Wu offered broader coverage, including the ancestral Wuhan strain and emerging variants like JN.1. These findings underscore the adaptability of NDV-based platforms in addressing the evolving SARS-CoV-2 landscape and reaffirm the ongoing utility of the ancestral Patria vaccine. Together, they demonstrate the potential of these platforms to drive the development of next-generation vaccines tailored to emerging viral threats, contributing to global health equity.

immunology↗

bioRxiv2020

Rapid and cost-effective development of stable clones for the production of anti-Ebola monoclonal antibodies in HEK293T cells

The Ebola virus (EBOV) disease has caused serious and recurrent epidemics in recent years, resulting in a fatality rate of nearly 50%. The most effective experimental therapy against the EBOV is the use of monoclonal antibodies (mAbs). In this work, we describe the development of HEK293T cells engineered for the transient and stable expression of mAb13C6, a neutralizing anti-EBOV monoclonal antibody. We transfected the HEK293T cells with a tricistronic vector to produce the heavy and the light chain of the antibody 13C6 and intracellular Green Fluorescent Protein (GFP) using Lipofectamine 3000. We then selected the transfected cells using puromycin pressure, dilution cloning, and cloning disks. This integrated strategy generated mAb-producing cells in 7 days with a transient expression of [~]1 mg/L. Stable pools were produced after 4 weeks, with expression levels of [~]0.8 mg/L. Stable clones with expression levels of [~]1.8 mg/L were obtained within 10 weeks. The produced antibodies exhibited the expected functionality; they recognized the GP glycoprotein of the Ebola virus in both ELISA assays and cell binding experiments using HEK293T cells engineered to express the EBOV GP at their membrane surface. By the combined use of GFP and the set of selection techniques here described, we drastically reduced the time from transfection to stable clone generation without resorting to costly equipment. In outbreaks or emergencies, this platform can significantly shorten the development of new biopharmaceuticals and vaccines.

bioengineering↗